POS0256 CLINICAL PREDICTORS OF ATTENUATED ANTIBODY RESPONSE TO PRIMARY SARS-CoV-2 VACCINATION IN A LARGE PROSPECTIVE STUDY OF PATIENTS WITH RHEUMATIC AND MUSCULOSKELETAL DISEASES
Authors: C. Connolly, T. P. Y. Chiang, M. Teles, S. Frey, J. Alejo, A. Massie, L. Christopher Stine, W. Werbel, D. Segev, J. Paik
Journal: Annals of the Rheumatic Diseases (2022)

Background An attenuated humoral response to SARS-CoV-2 vaccination has been observed in some patients with rheumatic and musculoskeletal diseases (RMD) (1). We sought to identify clinical factors associated with poor humoral response following primary (two-dose mRNA or single adenoviral vector dose) SARS-COV-2 vaccination in patients with RMD on immunosuppression. Objectives To identify clinical predictors of an attenuated antibody response to primary SARS-CoV-2 vaccination in RMD patients on immunosuppression. Methods We included patients ≥18 years old with RMD on immunosuppression who received either two-dose mRNA or single dose Janssen/Johnson and Johnson (J&amp;J) vaccination. Demographics, diagnoses, and therapeutic regimens were collected via participant report; those with prior COVID-19 infection were excluded. One month after vaccination, participants underwent SARS-CoV-2 antibody testing on the semi-quantitative Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay, which measures antibody to the SARS-CoV-2 S-receptor binding domain (RBD) protein (ceiling &gt;250U/mL later expanded to &gt;2500U/mL). Associations were evaluated using Fisher’s exact and Wilcoxon rank sum tests. Logistic regression analyses were performed to evaluate for clinical factors associated with antibody response. We adapted survival methods to address right-truncation of titers; this methodology was used to calculate medians. Participants provided informed consent electronically and the study was approved by the local Institutional Review Board. Results We studied 1138 RMD participants on immunosuppression; most were female (93%) and white (91%) (Table 1). One-hundred and fifteen (10%) had anti-RBD response in the negative range at a median (IQR) of 29 days (28-34) following completion of vaccine series. A greater proportion of participants with negative response were non-white, received J&amp;J vaccine, reported use of mycophenolate, rituximab, or glucocorticoids. Antibody response differed by immunosuppressive regimen, with those receiving rituximab having poorest response (Figure 1). Use of mycophenolate (aOR 9.92, p=0.001), rituximab (aOR 56.99, p=0.001), glucocorticoids (aOR 2.99, p=0.001) or receipt of J&amp;J (aOR 3.13, p=0.039) were associated with negative antibody response. Table 1. Clinical characteristics stratified by anti-SARS-CoV-2 RBD response Negative (n=115)* Positive (n=1023)* p-value† Age,median(IQR ) 49(42, 58) 47(37, 58) 0.07 Female sex,no.(% ) 108(94%) 952(93%) 0.78 Non-white,no.(% ) 16(13.9%) 83(8.1%) 0.04 Diagnosis,no.(% )Inflammatory arthritis 22(19.1%) 469(45.8%) &lt;0.01 SLE 27(23.5%) 193(18.9%) 0.27 Sjὅgren’s syndrome 5(4.3%) 46(4.5%) 0.53 Myositis 13(11.3%) 49(4.8%) &lt;0.01 Systemic sclerosis 2(1.7%) 9(0.9%) 0.55 Vasculitis 12(10.4%) 16(1.6%) &lt;0.01 Overlap connective tissue disease¶ 34(29.5%) 24(23.6%) 0.65 Vaccine,no.(% ) Pfizer/BioNTech 66(57.4%) 548(53.6%) 0.01 Moderna 38(33.0%) 438(42.8%) J&amp;J 11(9.6%) 37(3.6%) Non-biologic in regimen 89(77.4%) 725(70.9%) 0.52 Biologic in regimen 84(73.0%) 570(55.7%) 0.01 Mycophenolate** 56(48.7%) 120(11.7%) &lt;0.01 Rituximab 54(47.0%) 29(2.8%) &lt;0.01 Glucocorticoid** 61(53.0%) 284(27.8%) &lt;0.01 Withheld immunosuppression 18(21.2%) 260(39.6%) &lt;0.01 * Negative defined as anti-RBD titer &lt;0.8 U/mL. † Comparisons between negative and positive groups. ¶ Denotes a combination of two or more of the above conditions ** Mycophenolate: mycophenolic acid and mycophenolate mofetil. Corticosteroid: prednisone and prednisone equivalents Figure 1. Conclusion Use of mycophenolate, glucocorticoids, rituximab and receipt of J&amp;J vaccine were the strongest predictors of an attenuated antibody response to primary SARS-CoV-2 vaccination; these data support use of an additional primary dose in RMD patients. References [1]Deepak P, Kim W, Paley MA, et al. Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2: A Prospective Cohort Study. Ann Intern Med . 2021. Acknowledgements We would like to acknowledge the contributions of: Brian J. Boyarsky MD, PhD, Jake A. Ruddy BS, and Jacqueline M. Garonzik-Wang MD PhD. Disclosure of Interests Caoilfhionn Connolly: None declared, Teresa Po-Yu Chiang: None declared, Mayan Teles: None declared, Sarah Frey: None declared, Jennifer Alejo: None declared, Allan Massie: None declared, Lisa Christopher Stine Consultant of: Janssen, Boehringer-Ingelheim, Mallinckrodt, EMD-Serono, Allogene, and ArgenX., William Werbel: None declared, Dorry Segev Speakers bureau: Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallincrodt, Thermo Fisher Scientific, Regeneron, and Astra-Zeneca, Consultant of: Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallincrodt, Thermo Fisher Scientific, Regeneron, and Astra-Zeneca, Julie Paik: None declared